The present invention relates generally to systems of determining or monitoring the condition of hyperpolarized gas, such as monitoring the polarization level of the hyperpolarized gas during transport. The hyperpolarized gases are particularly suitable for MR imaging and spectroscopy applications.
Inert gas imaging (xe2x80x9cIGIxe2x80x9d) using hyperpolarized noble gases is a promising recent advance in Magnetic Resonance Imaging (MRI) and MR spectroscopic technologies. Conventionally, MRI has been used to produce images by exciting the nuclei of hydrogen molecules (present in water protons) in the human body. However, it has recently been discovered that polarized noble gases can produce improved images of certain areas and regions of the body, which have heretofore produced less than satisfactory images in this modality. Polarized Helium-3 (xe2x80x9c3Hexe2x80x9d) and Xenon-129 (xe2x80x9c129 Xexe2x80x9d) have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases are sensitive to handling and environmental conditions and can, undesirably, decay from the polarized state relatively quickly.
Various methods may be used to artificially enhance the polarization of certain noble gas nuclei (such as 129Xe or 3He) over the natural or equilibrium levels, i.e., the Boltzmann polarization. Such an increase is desirable because it enhances and increases the MRI signal intensity, allowing physicians to obtain better images of the substance in the body. See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure of which is hereby incorporated by reference as if recited in full herein.
A xe2x80x9cT1xe2x80x9d decay constant associated with the hyperpolarized gas""s longitudinal relaxation time is often used to characterize the length of time it takes a gas sample to depolarize in a given situation. The handling of the hyperpolarized gas is critical because of the sensitivity of the hyperpolarized state to environmental and handling factors and thus the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, e.g., delivery to a patient for imaging. Processing, transporting, and storing the hyperpolarized gasesxe2x80x94as well as delivering the gas to the patient or end userxe2x80x94can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic field gradients, surface-induced relaxation, hyperpolarized gas atom interactions with other nuclei, paramagnetic impurities, and the like.
Multiple relaxation mechanisms can arise during production and transport of the hyperpolarized gas. These problems can be particularly troublesome when transporting the hyperpolarized gas from a production site to a (remote) use site. In transit, the hyperpolarized gas can be exposed to many potentially depolarizing influences. Indeed, the polarized state of the gas can be unknowingly destroyed and undesirably transported to a use site in a clinically ineffective polarized state.
There is, therefore, a need to be able to monitor the status of the hyperpolarized gas and/or its environment during transport or storage so as to minimize exposure to depolarizing effects during transport. Improved monitoring methods and systems are desired so that more accurate measurements can be achieved and/or so that the hyperpolarized product can retain sufficient polarization to allow effective imaging at delivery when transported over longer transport distances in various (potentially depolarizing) environmental conditions and for longer time periods from the initial polarization than has been viable previously.
It is therefore an object of the present invention to provide a portable monitoring system which can determine the polarization level of the hyperpolarized gas (and/or hyperpolarized gas products) during transport.
It is another object of the present invention to provide a monitoring system that can automatically adjust a magnetic holding field to a predetermined or optimal value. By so doing, the resonant frequency of the gas can be shifted above that of potentially substantially depolarizing environmental conditions during movement of the hyperpolarized gas products from a production site to a remote use site, thus increasing the usable lifespan of the hyperpolarized gas products.
It is also an object of the present invention to provide a portable monitoring system that is configured to engage with a portable transport unit or shipping container for transporting a quantity of hyperpolarized gas therein.
It is a further object of the present invention to provide a portable system which can provide information to a user and which allows user input to react to the information about gas-related parameters, thereby allowing a user to be alerted to and thus take action to reduce the likelihood of any introduction of substantially depolarizing factors onto the hyperpolarized gases (such as unprotected exposure to stray magnetic gradients).
It is another object of the present invention to provide a method for determining the polarization level of a quantity of hyperpolarized gas at successive intervals in time to determine the effectiveness of the hyperpolarized product and to determine the overall polarization decay rate.
It is yet another object of the present invention to provide a method of reliably identifying gas polarization values corresponding to a quantity of hyperpolarized gas during transport and/or at a destination site, particularly in the presence of stray magnetic fields.
It is an additional object of the present invention to provide a method for determining the polarization of the gas in a manner which accounts for NMR coil resonance to more accurately measure the polarization level of the gas.
These and other objects of the present invention are provided by a portable monitoring system for determining the polarization of hyperpolarized gas in transit. The method includes transporting a quantity of hyperpolarized gas from a first site to a second site and intermittently transmitting a predetermined excitation pulse to the quantity of hyperpolarized gas during the transporting step. An NMR signal corresponding to the response of the hyperpolarized gas to the excitation pulse is received. The magnitude of this signal is then multiplied by a calibration factor and the level of polarization of the hyperpolarized gas is determined. The method also preferably includes the step of selecting the excitation pulse such that a plurality of transmitted pulses are substantially non-depolarizing to the quantity of hyperpolarized gas. In a preferred embodiment, the received signal is analyzed and a frequency-dependent correction factor is applied to adjust the signal polarization value to compensate for any externally-induced frequency shift that may appear in the measured signal value.
Another aspect of the present invention is directed toward a portable monitoring system for determining the polarization level of a quantity of hyperpolarized gas product. The system includes positioning a NMR coil proximate to a quantity of hyperpolarized gas product packaged for transport from a first site to a second site and transmitting an excitation pulse to the NMR coil to, in turn, excite the hyperpolarized gas product. A signal corresponding to the response of the hyperpolarized gas product to the excitation pulse is received by the NMR coil and the response signal is analyzed to determine the polarization level of the hyperpolarized gas product during transport. The system also includes an adjustment means for compensating the magnetic field strength associated with a magnetic holding field that is positioned such that it is operably associated with the quantity of hyperpolarized gas during transport. In a preferred embodiment, the adjustment means can be used to alter the magnetic field so that a transmit and receive frequency used for monitoring the gas corresponds to an optimal value associated with the NMR coil resonance.
In a preferred embodiment, the hyperpolarized gas product is held within a transport unit having a cylindrically or longitudinally extending solenoid coil used to generate a magnetic holding field for the hyperpolarized gas. Also preferably, the portable monitoring system includes a current input adjustment means which is configured to compensate for detected magnetic holding field strength fluctuations (such as to change or increase the current into the solenoid used to generate a magnetic holding field for the hyperpolarized gas or product held in a chamber therewithin to optimize the field strength of the magnetic holding field).
An additional aspect of the present invention is a computer program product for monitoring and/or determining the polarization level of a hyperpolarized gas product. The computer program product comprises a computer readable storage medium having computer readable program code means embodied in said medium, the computer readable program code means comprising a computer readable program code means for selecting an excitation pulse. The program also includes a computer readable program code means for transmitting the selected excitation pulse to a quantity of hyperpolarized noble gas product and a computer readable program code means for analyzing a signal associated with the response of the hyperpolarized noble gas product to the excitation pulse. The program further includes a computer readable program code means for compensating the response signal such that it more accurately corresponds to the hyperpolarization level of the gas and a computer readable program code means for determining the polarization level of the hyperpolarized gas.
In a preferred embodiment, the computer program product also comprises a computer readable program code means for generating a correction factor table corresponding to a Fourier transform of an NMR coil response and a computer readable program code means for applying a correction factor corresponding to the frequency of a measured response to produce a corrected value.
Another aspect of the present invention is directed to a portable transport unit for hyperpolarized gas in combination with monitoring apparatus. The apparatus comprises a portable transport unit configured to hold a quantity of hyperpolarized gas therein and a NMR coil configured and sized to be positioned in a portable transport unit such that it is proximate to a quantity of hyperpolarized gas product. The apparatus also includes a pulse generator for generating an excitation pulse. The apparatus additionally includes transmit and receive means operably associated with the pulse generator and the NMR coil. The transmit means transmits the excitation pulse to the hyperpolarized gas via the coil and the receive means receives a signal corresponding to the response of the hyperpolarized gas to the transmitted excitation pulse. A signal analyzer is operably associated with the receive means. The analyzer includes a computer readable program code means for determining the polarization level of the hyperpolarized gas during transport.
In a preferred embodiment, the combination monitoring system and portable transport unit comprises a solenoid configured to generate an adjustable electromagnetic holding field proximate to the quantity of hyperpolarized gas and the adjustability of the holding field corresponds to the current input to the solenoid. The present invention is advantageous because the monitoring system is portable and readily engaged to a transport device. Further, the portable monitoring system can correct for environmentally-induced signal shift and yield a more accurate T1 value for the hyperpolarized gas. In addition, the portable monitoring system can provide feedback about ambient conditions or about temporal magnetic holding field variations and allow for the adjustment of same to minimize the depolarizing effects attributed to stray magnetic fields, especially deleterious oscillating fields which can easily dominate other relaxation mechanisms. Preferably, the monitoring system can automatically adjust the current provided to the solenoid that generates the magnetic holding field. The automatic adjustment (and/or with user input) can shift the strength of the magnetic holding field according to external or internal (circuitry) parameters; for example, to shift the resonance frequency of the hyperpolarized gas away from an external deleterious event (such as a proximate static magnetic field). In addition or alternatively, the monitoring system can detect field drift due to temperature-induced resistance variation in the coil(s) and adjust the current input to the solenoid to maintain the desired field strength. Further, the monitoring system can verify the level of polarization at the destination site providing an easy inspection device for receiving inspection purposes/delivery verification. Indeed, the monitoring system is preferably configured such that the hyperpolarized gas can be analyzed within the transport unit such that the hyperpolarized gas can be checked both during transit and at the end use site without removing the relatively fragile gas container from the transport unit. Advantageously, the monitoring system can verify via an on-board portable non-destructive test (NDT) method, that the transported product meets the applicable polarization level standard at an incoming/receiving inspection dock and/or immediately prior to use.